四溴双酚A（TBBPA）是目前全球范围内使用量及应用范围最大的溴代阻燃剂，通过大气干湿沉降，河流输入等多种渠道进入到湖泊水体和沉积物中，通过鱼类的呼吸及摄食作用进入到鱼体内。由于TBBPA脂溶性的特点使其易于被鱼类吸收并累积，对人类健康存在潜在威胁。本研究调查了巢湖水体、沉积物及鱼体内TBBPA的时空分布规律，结合TBBPA对鱼类毒性靶器官的研究，选择谷胱甘肽硫转移酶（GST）、谷胱甘肽还原酶（GR）、尿二葡萄糖醛酸转移酶（UDPGT）、谷丙氨酸转氨酶（ALT）和谷草氨酸转氨酶（AST）酶学指标和血清蛋白，进行TBBPA对鲫鱼毒性效应响应的分析，由此筛选出敏感有效的监测TBBPA的生物标志物。本研究通过对TBBPA在巢湖表层沉积物的吸附解吸特征研究表明，沉积物对TBBPA有较强吸附能力，吸附行为主要为物理表面吸附。pH 为11.5，温度为30℃时TBBPA的吸附量与解吸量达到动态平衡，夏季巢湖水华暴发时湖泊的理化及气象条件有利于 TBBPA大量解吸到上覆水中，对水生生物造成潜在毒害威胁。根据对巢湖12个采样点周年水体、沉积物（分层）TBBPA含量调查，掌握了湖泊不同介质中TBBPA时空分布特征。对巢湖7月、9月和11月3季的水体TBBPA含量检测表明，TBBPA浓度在0.73 - 4.77 μg/L之间，最高值4.77 μg/L出现在7月份的4号样点。TBBPA在巢湖垂直分层的沉积物中由表层（0 - 2 cm）为155 ng/g dry weight到底层（7-15 cm）88 ng/g dry weight逐渐降低。巢湖表层沉积物TBBPA含量较高的点均位于污染较重的入湖河流入口处，主要来源为入湖河流的输入，在空间上由西向东逐渐扩散减小。巢湖4种鱼类鲤鱼（Cyprinus carpio）、鲫鱼（Carassius auratus）、鲶鱼（Silurus asotus）、翘嘴红鲌（Culter alburnus）器官组织TBBPA平均含量排序为鲶鱼>鲤鱼 >鲌鱼>鲫鱼，但各鱼种间TBBPA平均含量差别较小，为28.53 - 39.39 ng/g。鲤鱼肾脏TBBPA含量与其体重呈正相关，鳃、腹、背和卵及肝脏无显著相关关系。根据对绿藻、大型溞和鲫鱼急性毒性试验结果，计算得到绿藻的96 h的EC50为0.705 mg/L，大型溞LC50为0.158 mg/L，鲫鱼LC50为3.531 mg/L，TBBPA对鲫鱼具有中高度毒性。结合文献数据，推算TBBPA的安全阈值为1.80 μg/L，7月份巢湖水体具有一定的生态风险，其他季节没有明显风险。TBBPA慢性暴露的0.5 mg/L处理组鲫鱼肝组织切片未见明显病变。肾脏有弥散性沉积，但肾小球病变不显著；鳃小片上皮细胞轻度增生，部分伴有鳃小片细胞的脱落，后期有融合现象；在TBBPA2.0 mg/L暴露组，随着暴露时间延长肝细胞肿胀严重，肝细胞出现弥散且索状结构被破坏，暴露32 d后，肝细胞肿胀扩展到整个肝，细胞基质大量丢失，胞核固缩（坏死）；肾小球毛细血管明显萎缩，甚至坏死；鳃小片上皮细胞的大面积增生，致使数条鳃小片融合在一起。慢性TBBPA暴露后，鲫鱼肝脏和肾脏均表现出时间-剂量-依赖性的病理损伤，而两剂量组卵巢未发现明显病变。急性TBBPA暴露下鲫鱼肾脏和肝脏均表现为剂量依赖性关系，为TBBPA作用的靶器官。精巢在急性TBBPA暴露下病理损伤严重。TBBPA分布动力学研究表明，肝脏和肾脏是TBBPA含量最高的部位；低浓度0.5 mg/L组TBBPA暴露下鲫鱼肾脏和肝脏具有很强的生物富集能力，并在第8 d达到最高值。与0.5 mg/L暴露浓度相比，2.0 mg/l的高浓度组肾脏和肝脏富集TBBPA能力急剧下降，但TBBPA绝对含量仍高于低浓度组，鳃和肌肉组织中TBBPA含量增高，表明此浓度TBBPA胁迫造成肝肾富集机能受损，进而加大TBBPA进入血液的机会，导致处于分布末端不具富集能力的组织，如鳃和肌肉TBBPA含量增加。对5种酶活变化的综合分析表明，慢性TBBPA暴露下，鲫鱼肝脏受到外来污染物胁迫时首先发生应激反应，血清中的酶活继而因接收各组织器官的代谢产物而出现变化。AST和ALT在肝脏中活性同时下降，并在血清中滞后性升高。其中2.0 mg/L组血清中两酶活性升高时间早于0.5 mg/L组；肝脏中GR和GST活性则显著升高，高浓度组血清GR和GST随之升高，其中高浓度组由于诱导强度大，血清变化的时间滞后趋势不明显。UDPGT作为II相代谢中重要的代谢酶，有可能通过催化UGA与TBBPA的直接结合被迅速大量消耗，肝脏中的UDPG活性被严重抑制，这可能引起鲫鱼与UDPGT相关的类固醇和激素类，如甲状腺激素代谢紊乱。利用凝胶成像分析仪对鲫鱼血清蛋白电泳条带进行分析，不同时间组的鲫鱼血清蛋白可以被分为11个较易区分的组分，发现TBBPA胁迫鲫鱼的血清蛋白中一个重要差异表达蛋白，为组分11，分子量约为24 Kda。通过对TBBPA染毒暴露鲫鱼组织学、分布动力学、酶学及血清蛋白组分的分析，发现鲫鱼在第8 d达到代谢高峰。0.5mg/L处理组在此后的第16 d至32 d各项指标逐渐恢复到与对照相当，而2.0 mg/L的高浓度处理组各项指标均较对照异常，表明TBBPA暴露鲫鱼自身代谢平衡可恢复阈值应在0.5 - 2.0 mg/L之间。经对5个生物转化酶和血清蛋白11个组分的对比分析，最终选定对TBBPA暴露敏感生物转化酶GST和血清蛋白组分11作为检测TBBPA污染的生物标志物。

Tetrabromobisphenol A (TBBPA) is the largest one of BFRs in using quantity and area. It can enter into water body and sediment through dry and wet deposition and inflow revers. Further it can be ingested or respaired into fish body. TBBPA was easy to absorbed and bioaccumulated by fish for its lipophlic which brings some potential health risk for human being. This study has investigated the spatio-temporal distribution of TBBPA of water, sediment, and fish body in Lake Chaohu. Combining LC50(EC50) abtained in acute test we designed the available TBBPA concentrations in chronic test to exposure to Carassius auratus. Five enzymes including glutathione S- transferase (GST), glutathione reductase (GR), Urinary glucuronic acid transferase Ⅱ(UDPGT), glutamic oxaloacetic transaminase (AST), and glutamic pyruvic transaminase were chose to analyse the effect on Carassius auratus and screened some of them as biochemical markers to monitor TBBPA pollution speedly and sensitively.Sorption and desorption characteristic of sediment in Lake Chaohu was discussed. Results showed that the surface sediment had strong ability absorbing TBBPA. Sorpting function was mainly phyicical surface sorption. Another it reached the equilibrium between sorption and desorption quantity at pH=11.5 and 30℃ which is the right physical and meteorologic condition of water-bloon bursting in Lake Chaohu. Under that condition TBBPA is easily to desorp into surface water to bring potential harm aquatic animals.According to the annual investigation of TBBPA concentration in water, sediment, and fishes from 12 sample sites the spatio-temporal distribution character of different medium in Lake Chaohu was depicted. TBBPA concentration on July, September, November was in the range of 0.73-4.77μg/L. The highest one was 4.77μg/L emerging on July at 4th sample site. The concentrations of TBBPA in sediment decreased from the surface to bottom layer where it was 155 ng/g dry weight for 0-2 cm depth sediment, 110 ng/g dry weight for 2-7 cm, 88 ng/g dry weight for 7-12 cm, respectively. The highest values was presented at locations 3, 4, 5, and 6 which are situated at the entrance of Nanfei and Shiwuli River which are the most heavily polluted inflow river of Lake Chaohu. TBBPA concentration is gradually decreasing from west to east.TBBPA was measured in different organs and tissues from four fish species. Results showed that the average concentrations of TBBPA in tissues of Cyprinus carpio and Silurus asotus were higher than those in Culter alburnus and Carassius auratus. The mean concentration of the four species are in the ranged of 28.53 - 39.39 ng/g dry weight (whole), but the differences among species were not significant.TBBPA concentration in kidney of Cyprinus carpio had a rising trend with weight increasing. That was not found in gill, adipose, muscle, and spawn obviously.The results from acute test showed that 96h EC50 of Scenedesmus quadricauda was 0.705mg/L, 0.158mg/L for Daphnia, 3.531mg/L for Carassius auratus. The toxicity of TBBPA belong to the upper grade.Pathological changes were not found in Chronic TBBPA exposure test of 0.5 mg/L. Kidney had a little dispersal deposit. But pathological changes of glomerular was not significance. Epithelial of gill lamellae was lightly hyperplasia with some gill lamellae falling off. It melted at late exposure period. Liver cells swelled heavily with time lasting. Its cord-like structure was detryed and dispered at 2.0 mg/L TBBPA concentration. Swelling of liver cells extend to whole liver, extracellular matrix missing massively, condensation nuclei (necrosis), glomerular athrophy after 32d exposure. Epithelial of gill lamellae proliferated massively to lead to gill lamellae melting together. Pathological changes of ovarian not found. The effect on liver and kidney was dosage depended as TBBPA exposure to Carassius auratus. Liver and kidney were target organs of TBBPA, and he testis was destroyed heaveyly at acute test.According to distribution dynamics of TBBPA in Carassius auratus the highest concentration was in liver or kidney. Those had strong ability to accumulate TBBPA and reached to peak value day 8 at 0.5 mg/L. To compare with 0.5mg/L, the accumulation ability of liver and kidney decreased quikly at 2.0 mg/L. But its absolute concentration was still higher than that of low concentration group.Meantime the concentration in gill and musle increased. That indicated that the bioaccumulative mechanism was damaged. That led to TBBPA entering into blood, and distributing more TBBPA into gill and muscle which was the bottom of blood transportation no bioaccumulate function. Stress response first happened in liver of Carassius auratus in chromic TBBPA exposure test. After that the activity of enzyme in blood appeared some change for accepting metabolites from other organs. The activity of AST and ALT all decreased in liver and then increased in serum lately. The time point of rising at 2.0 mg/L was a little earlier than at 0.5 mg/L. The avtivity of GST and GR rised significansly. The same thing happened in serum for GST and GR. The trend of time-delay effect in serum was not obviously as induceing severly. As the most important metabolism enzyme UDPGT maybe consumed largely by its catalyzing the conbining between UGA and TBBPA. Then the activity of UGPGT in liver suppressed severly to lead to disorder of steroid and hormone, like thyroid hormone related to UDPGT.11 th components of electrophoresis bands of serum protein was easily distinguished by using Gel Image Analysis System. An important differtial expression protein named 11th component was found. Its molecular weight was about 24kdaCombining histology, distribution dynamics, enzymology, and serum protein analysisi together it reached metalolism peak day 8 in chronic TBBPA exposure test at 0.5 mg/L. After that most indexes recovered to be closed to control f. But there was abnormity of most indexes at 2.0 mg/L to compare with control. Those implicated that the range of recovery was from 0.5 to 2.0 mg/L to keep its etabolism dynamic equilibrium of TBBPA.This study has selected GST and componet of 11 in serum protein as biomarker to detect TBBPA pollution.